Discovery supports theory of Alzheimer's disease as form of diabetes

www.physorg.com ^ | 11/26/2007 | Northwestern University

[Red Badger]

Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer’s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer’s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for “amyloid ß-derived diffusible ligand.”)

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer’s disease, the Northwestern study sheds light on the emerging idea of Alzheimer’s being a “type 3” diabetes.

The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer’s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)

In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer’s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.

“We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. “Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer’s disease.”

ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible.

In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.

“We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer’s brains,” said Klein, a member of Northwestern’s Cognitive Neurology and Alzheimer's Disease Center. “We’re dealing with a fundamental new connection between two fields, diabetes and Alzheimer’s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.”

Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.

They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.

“In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,” said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein’s lab. “These factors suggest that insulin resistance in the brains of those with Alzheimer’s is a response to ADDLs.”

“With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer’s treatment,” said Klein. “I think such drugs could supercede currently available Alzheimer’s drugs.”

Source: Northwestern University

[Taffini]

i don’t drink. what taste good? what is good for you? the red i hear. what about two buck chuck? i don’t want swill, but can’t afford the fine line either.

[Marie]

Honestly, I feel great on a low carb diet. (It's just boring.) The trick is to eat LOTS of veggies and to not go overboard with the meat and fat.

Here's "Marie's Rule of Thumb". Look at the palm of your hand. You want to eat *that* amount of protein 4-5 times a day. And it shouldn't *all* be red meat. Chicken, fish, red meat, game meat, eggs, cheese, nuts, seeds... it's all good.

Now cup your hand. You should eat *at least* that amount of veggies 4-5 times a day. If you're borderline Type 2 diabetic with a family history of the disease (darn Indians!), eat that same amount of fruit (a handful) 3x a week for vitamin C.

Do I do this all the time? Nope. I've been rotten to myself for awhile now. And I'm starting to have prediabetic symptoms again. I've turned this ship around before and I know I can do it again. I'm adding vitamins, minerals, metformin and plenty of water to the mix. NOTHING ARTIFICIAL.

In about two months I'll be healthy as a horse.

Now... if I can only keep from falling off that stupid horse down the road, I'll be fine! ;-) (Sometimes you just want a freakin' stuffed potato.)

ONE MORE THING: Everything I just said is for ME. With my genetic disposition, my lifestyle, my health issues; this is the perfect diet for Marie. I do NOT believe that there is one diet which is perfect for everyone. Some people get sick off carbs, some can't handle fat. Some can't stand meat products. Some just need a slightly modified ratio and some have iron constitutions and do just fine with whatever they throw down their maw.

But I do believe that people misunderstand and abuse the low-carb diet. This confuses the situation and cheats the folks who really do need it.

[Global2010]

Thanks for the Ping Island Jeff guy.

(gettin’ kind a cold here on the PNW coast huh, my lab just swiped me with his big wet honker and I was enjoying a REAL not from concentrate flavored Orange smoothie for dinner)

[Varda]

I don’t know about Parkinson’s but ketogenic diets have been used for years to defeat/improve epilepsy.

[Varda]

You were right. I keep away from most carbs and try to stay with as natural a diet as I can. Grass fed beef is just as healthy as wild game meat and has the same omega-3 carcass fat. I used to raise my own grass fed lamb and it tasted better than anything you could get in a store. I occasionally eat fruit (in season) but vegetables are an every day item. No beans, corn, or peas though. I pretty much stick with green leafy ones, broccoli and the like.

[texas booster]

http://www.freerepublic.com/focus/f-chat/1897355/posts

All, please take a look over at the Folding@home thread. Folding@home is a computer simulation that you download to your computer that runs in the background when nothing else is happening.

The goal is to try an replicate protein folding to find a cure for Alzheimer’s and Parkinson’s Disease, among others.

Please ping if you have any questions!

Thank again, Jeff, for the diabetes ping!

We may yet figure out this disease.

[Varda]

Actually a high fat/moderate protein/low carb diet won’t make you sick unless you have some other condition that precludes it.

For my family, it makes the difference between being on drugs and not being on drugs. Everyone I know who has tried it has expressed wonder at how much better they feel. When I fall off the low carb wagon, I get a flare up of arthritis. Go back to low carb and the joint problems go away. This is just a bonus side effect for me.

[Varda]

“isn’t your brain just full of fat”

This is correct and it’s one reason babies need a high fat diet. Their brains are growing! I knew this when I raised animals. Mammal babies need a high fat diet to thrive. I had to constantly check on people who bought animals from me to make sure they weren’t falling prey to the low-fat propaganda.

[Varda]

I go for moderately priced reds. Australians mostly but we’ve gotten a Portuguese one recently that’s pretty decent.

[mad_as_he$$]

Nice job!!! That takes discipline and determination.

[Primetimedonna]

Thanks for the ping, Jeff! Was going to tell you something, but I forgot what! ;>)

[Freedom2specul8]

Several sources do say that keeping blood sugar low by not eating empty carbs will supposedly help keep insulin resistance (also referred to as metabolic syndrome) from developing into diabetes.

http://www.medicinenet.com/insulin_resistance/article.htm

google search

[Freedom2specul8]

have you tried various spices along with perhaps onions (of your choosing) with zuccini, red/yellow bell peppers etc. in your eggs w/maybe a bit of ham? (I use to use 1 egg and 2 eggwhites along with a mixture of the previous) Also, diet pop is not good for insulin resistance..apparently, the ‘fake sugar’ is hard on the body to metabolize. drag eh?

[Marie]

I love your idea of eating less yolks. I think part of the problem with the LC diet is that it typically has too much fat. Fat suppresses the appetite and you just get sick of eating after awhile.

Next week I'm making dehydrated veggie chips and jerky!

[Freedom2specul8]

That sounds yummy...i love jerky. I've been thinking about dehydrating onions....am assuming it would be easy, but stinky for awhile. ;-) I purchased a large container of dehydrated garlic, and boy does that save time in preparation. for the past 10 yrs I've developed an intolerance to a lot of fatty meats...because I switched to fish and chicken. The fat sometimes just makes me nauseous. However, I just read that unless the fish is grown wild and not on farms, it's benefits are reduced. I was like great....and now they tell us? ((SIGH)) BTW, it may just be me, so I don't know if it works for everyone...but I sometimes eat maybe 15 almonds prior to a meal, and it suppresses my appetite.

I've read that protein sugars sustain energy longer than carbs etc... so lowfat yummy proteins may help insulin resistance. I was told I had it around 2000, later found out it was a misdiagnosis and not proven by blood tests...once I got educated (we HAVE to be our on advocates) I found out that I had thyroid cancer and it caused so many problems. Once I got the thyroid removed, my metabolism improved, lost 20lbs quickly and my engery level incresed. Am still losing weight and love the new energy level. I give God the credit for finding a lot of the info, because I prayed for help bigtime. :D

[Petronski]

Wow.

[Scythian]

Kind of makes sense, it seems to be increasing dramatically about the same time and in proportion to diabetes. Western living is dangerous indeed ...

[Age of Reason]

Very healthy.

Good for you.

[neverdem]

comment 49 from you:

Unless the FDA continues to black label and ban those pharmacueticals that do the job best.

Troglitizone.....removed from the market.
Rosiglitizone (Avandia) .....black labeled.
Pioglitizone (Actos) ....the next one to go?

comment 53

Don't panic. Actos works differently than Avandia and is so far not targeted for any action.

Why did you write that? Aren't they all thiazolidinediones, also known as insulin sensitizers?

IMHO, these drugs were given to folks with the wrong genotype. Drug Makers Seek Clues to Side Effects in Genes

[xJones]

Me, too. But ... I have learned to make almost everything I love to eat (bread, waffles, cereal, cheesecakes, etc.) with very few carbs. And delicious, I might add.

What about chocolate ice cream? And don't even mention that tasteless carob bean substitute, or I may throw up in your general direction.:)